Action Points

Note that this AHA statement suggests that mid-life hypertension may lead to late-life dementia, and treatment of hypertension should be recommended on that basis (among others).

Be aware that, though the biological rationale for this statement is on firm-footing, the objective evidence of a hypertension-dementia causal link is lacking.

There is compelling evidence that chronic arterial hypertension in mid-life is associated with late-life dementia, including Alzheimer's disease, according to the authors of a scientific statement issued by the American Heart Association (AHA).

While review of the literature revealed insufficient data to make evidence-based recommendations, "judicious" and individualized control of hypertension is probably key, Costantino Iadecola, MD, director of the Brain and Mind Research Institute at Weill Cornell Medical College in New York City, and colleagues reported online in Hypertension.

Given the prevalence of hypertension and the fact that effective drugs are so accessible, "treatment of hypertension may prove to be one of the best ways to prevent or delay dementia," the AHA statement authors wrote.

They acknowledged, however, that the question of whether treating hypertension prevents or reverses cognitive decline remains unanswered. While observational studies have demonstrated that cerebrovascular damage caused by hypertension is cumulative, evidence that antihypertensive treatment improves cognition is not conclusive.

Also, the cognitive impact of late-life hypertension isn't clear, as some evidence has suggested that "in very late life, aggressive treatment may be more problematic than helpful," they wrote.

Their literature review showed that hypertension may promote Alzheimer pathology by leading to ischemic damage of white matter critical for cognitive function.

Although there is "substantial evidence that hypertension leads to cognitive impairment, an effect attributed to oxidative stress-driven cerebrovascular dysfunction and damage, the underlying cellular and molecular mechanisms remain incompletely understood," the authors wrote.

"New discoveries in the cellular and molecular pathology of the cerebrovascular tree and associated cells, coupled with the use of new imaging tools, biomarkers, and genomic-proteomic approaches in clinical trials, offer the prospect to address these unanswered questions and to develop new treatments to mitigate the devastating impact of hypertension on cognitive health," they added.

In addition to a need for more understanding of the basic science aspects, there's also a need for more work in the form of randomized controlled trials to test whether interventions can prevent dementia. Barriers to that kind of information have included difficulties doing the needed decades-long longitudinal studies as well as a lack of uniform cognitive outcomes across studies. The complex relationship between hypertension and cerebrovascular risk factors has hampered treatment assessment, the researchers said.

But Iadecola noted that clinical trials that specifically address the role of hypertension in cognitive dysfunction across the entire life course -- from infancy to late life -- are urgently needed.

"Such an effort needs to be coupled to basic science investigations addressing why and how hypertension exerts such powerful deleterious effects on cognitive function and its overlap in Alzheimer's disease and other forms of late life dementia," he told MedPage Today.

There are a number of challenges clinicians currently face in treating hypertension, including individualizing blood pressure targets, he added. In an era of "precision medicine," these targets need to be established on a patient-by-patient basis, Iadecola said, noting that in the elderly, lowering blood pressure can be detrimental.

Establishing the best time to initiate treatment, particularly when a patient's blood pressure falls into the "prehypertension" range of 120 to 139 mm Hg systolic, also remains a concern: "There is evidence that elevations in blood pressure in the prehypertension range are also associated with increased demential risk," Iadecola said. "Whether treatment initiated in this blood pressure range is effective remains to be established."

In the absence of contraindications, starting treatment "as soon as blood pressure starts to inch up," may be worthwhile, he suggested.

Control of hypertension is likely to be a fundamental step in the effort to reduce the incidence of AD and other forms of dementia worldwide, Iadecola said.